SMIP004-7 is a cell penetrant, potent and selective ubiquinone uncompetitive inhibitor of mitochondrial Complex I (NADH:ubiquinone oxidoreductase). SMIP004-7 selectively binds to a distinct N-terminal region of Complex I catalytic subunit NDUFS2, which leads to rapid disassembly of Complex I. SMIP004-7 potently inhibits growth of triple-negative breast cancer xenografts in mice.
cell penetrant, potent and selective ubiquinone uncompetitive inhibitor of mitochondrial Complex I
We previously identified SMIP004 (N-(4-butyl-2-methyl-phenyl) acetamide) as a novel inducer of cancer-cell selective apoptosis of human prostate cancer cells. SMIP004 decreased the levels of positive cell cycle regulators, upregulated cyclin-dependent kinase inhibitors, and resulted in G1 arrest, inhibition of colony
Metabolic targeting of cancer by a ubiquinone uncompetitive inhibitor of mitochondrial complex I
Trends in pharmacological sciences, 43(9), 706-708 (2022-04-07)
Targeting metabolic reprogramming has proven successful in oncology, but this field requires better identification of drugs that inhibit mitochondrial metabolism in cancer cells. Recent work from Dr Wolf's group reveals that the primary target of the antitumor compound SMIP004-7 is
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